Evidence map›Paper›PMID 26280574›Full record

ArticleThe Journal of clinical investigation2015

Mucosally transplanted mesenchymal stem cells stimulate intestinal healing by promoting angiogenesis.

Nicholas A Manieri, Madison R Mack, Molly D Himmelrich, Daniel L Worthley, Elaine M Hanson, Lars Eckmann, Timothy C Wang, Thaddeus S Stappenbeck

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Nicholas A Manieri
Madison R Mack
Molly D Himmelrich
Daniel L Worthley
Elaine M Hanson
Lars Eckmann
Timothy C Wang
Thaddeus S Stappenbeck
Washington University in St. Louis · USUniversity of California, San Diego · USUniversity of Adelaide · AU

Funding

Washington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Nicholas O. Davidson · 2000 to 2026
$30.8M
PRINCIPLES IN PULMONARY RESEARCHT32HL007317 · NHLBI · WASHINGTON UNIVERSITY · PI Steven Brody, Michael J Holtzman · 1985 to 2026
$16.1M
RESPONSES OF INTESTINAL STEM CELLS TO EPITHELIAL INJURYR01DK071619 · NIDDK · WASHINGTON UNIVERSITY · PI STAPPENBECK, THADDEUS S · 2008 to 2017
$3.2M
NHLBI NIH HHS T32 HL007317NIDDK NIH HHS DK07161907NIDDK NIH HHS P30 DK052574NIDDK NIH HHS P30DK052574NIDDK NIH HHS R01 DK071619
6 · The paper itself

Abstract

Mesenchymal stem cell (MSC) therapy is an emerging field of regenerative medicine; however, it is often unclear how these cells mediate repair. Here, we investigated the use of MSCs in the treatment of intestinal disease and modeled abnormal repair by creating focal wounds in the colonic mucosa of prostaglandin-deficient mice. These wounds developed into ulcers that infiltrated the outer intestinal wall. We determined that penetrating ulcer formation in this model resulted from increased hypoxia and smooth muscle wall necrosis. Prostaglandin I₂ (PGI₂) stimulated VEGF-dependent angiogenesis to prevent penetrating ulcers. Treatment of mucosally injured WT mice with a VEGFR inhibitor resulted in the development of penetrating ulcers, further demonstrating that VEGF is critical for mucosal repair. We next used this model to address the role of transplanted colonic MSCs (cMSCs) in intestinal repair. Compared with intravenously injected cMSCs, mucosally injected cMSCs more effectively prevented the development of penetrating ulcers, as they were more efficiently recruited to colonic wounds. Importantly, mucosally injected cMSCs stimulated angiogenesis in a VEGF-dependent manner. Together, our results reveal that penetrating ulcer formation results from a reduction of local angiogenesis and targeted injection of MSCs can optimize transplantation therapy. Moreover, local MSC injection has potential for treating diseases with features of abnormal angiogenesis and repair.

Indexed as

ColonIntestinal MucosaMesenchymal Stem Cell TransplantationNeovascularization, PhysiologicWound HealingWounds and InjuriesAllograftsAnimalsEpoprostenolMiceMice, KnockoutVascular Endothelial Growth Factor AEpoprostenolVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouse

Identifiers

PMID26280574
PMCPMC4588308
OpenAlexW2168312071

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.